| Autor: |
Rundgren IM; Department of Biomedical Laboratory Scientist Education and Chemical Engineering, Faculty of Engineering and Natural Sciences, Western Norway University of Applied Sciences, 5020 Bergen, Norway.; Department of Clinical Science, University of Bergen, 5020 Bergen, Norway., Ryningen A; Department of Biomedical Laboratory Scientist Education and Chemical Engineering, Faculty of Engineering and Natural Sciences, Western Norway University of Applied Sciences, 5020 Bergen, Norway., Anderson Tvedt TH; Section for Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway., Bruserud Ø; Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.; Section for Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway., Ersvær E; Department of Biomedical Laboratory Scientist Education and Chemical Engineering, Faculty of Engineering and Natural Sciences, Western Norway University of Applied Sciences, 5020 Bergen, Norway. |
| Abstrakt: |
Immunomodulatory drugs (IMiDs) are used in the treatment of hematological malignancies, especially multiple myeloma. IMiDs have direct anticancer effects but also indirect effects via cancer-supporting stromal cells. Monocytes are a stromal cell subset whose metabolism is modulated by the microenvironment, and they communicate with neighboring cells through extracellular release of soluble mediators. Toll-like receptor 4 (TLR4) is then a common regulator of monocyte metabolism and mediator release. Our aim was to investigate IMiD effects on these two monocyte functions. We compared effects of thalidomide, lenalidomide, and pomalidomide on in vitro cultured normal monocytes. Cells were cultured in medium alone or activated by lipopolysaccharide (LPS), a TLR4 agonist. Metabolism was analyzed by the Seahorse XF 96 cell analyzer. Mediator release was measured as culture supernatant levels. TLR4 was a regulator of both monocyte metabolism and mediator release. All three IMiDs altered monocyte metabolism especially when cells were cultured with LPS; this effect was strongest for lenalidomide that increased glycolysis. Monocytes showed a broad soluble mediator release profile. IMiDs decreased TLR4-induced mediator release; this effect was stronger for pomalidomide than for lenalidomide and especially thalidomide. To conclude, IMiDs can alter the metabolism and cell-cell communication of normal monocytes, and despite their common molecular target these effects differ among various IMiDs. |
